The goal of this project is to obtain a fundamental understanding of the conformations of nucleic acids and of the forces which govern them. We will seek useful correlations between the base sequence of a nucleic acid and its structure and biological function. A better understanding of nucleic acids may help in the prevention or cure of all diseases which depend on the functions of nucleic acids. These include viral diseases, genetic diseases and cancer. Oligonucleotides of specific base sequence will be synthesized to provide structural elements of DNA, RNA and DNA-RNA hybrids. Thermodynamics and kinetics of formation of complementary double-strand helices, mismatched helices and hairpin loops will be measured. Conformations will be determined in solution using one-and two- dimensional nuclear magnetic resonance measurements. Tertiary and higher-order folded structures in nucleic acids will be studied using absorption and scattering of circularly polarized light.